Open surgical revascularization defined as the improvement of blood supply to a body part or organ using a graft is performed in over 30 Mio patients around the world each year. Unfortunately, graft failure occurs in 20 to 50% of the cases within 5 years, mainly due to stenosis at the anastomosis site leading to occlusion [1].
In the case of endovascular intervention, medical devices have been identified to prevent intraluminal vessel stenosis such as stents or plain balloon with promising results. However, when open revascularization is mandatory, no platform is available for local drug delivery. Current post-open revascularization treatments imply repetitive oral dosing of the active compound(s) with the risk of side effects.
To increase the chance of reperfusion by avoiding the development of stenosis, a local preventive treatment applied at the site of the surgery would be safer and more efficient than systemic administration. To be efficient a local therapy needs to stay located at the site of administration and to deliver the drug(s) according to an optimal time schedule defined by the development of the pathology. This formulation needs also to be biocompatible and biodegradable to be eliminated via either hydrolysis or enzymolysis to avoid a second surgery to remove the drug delivery device. Furthermore, it should be delivered in a small volume, about 5 ml for humans and should not damage the graft or the surrounding tissues.
Even though the perivascular route of administration has been tested in animal models, the success of this approach has been limited. To date, no clinical application is yet available in the market. The reasons for this limited success lies in feasibility restrictions. So far, no formulation achieved long term local permanence at the diseased site, combined with optimal drug(s) release profile(s) fitting the development of the pathology, using biocompatible and biodegradable polymers for the preventive treatment of restenosis after open surgical revascularization.
These goals have been attained in the present invention by providing pharmaceutical formulations for use in the treatment and/or prevention of restenosis in a subject in need thereof in accordance with the present invention.